The thymus gland is vital to the normal development, and maintenance of the immune system and appears to be involved in the aging process. Experimental and clinical investigations of the past 15 years have provided evidence that the thymus has an endocrine function and secretes a family of hormonal-like polypeptides which influence immune function. One such family of peptides which were isolated and characterized by our group has been termed thymosin. The objective of this proposal is to study the endocrine role of the thymus gland during the aging process in order to determine whether it is possible to modulate and correct, via the administration of thymosin, the immune imbalance that often occurs with the aging process. This proposed study has the following specific objectives: (1) To evaluate the effect of long-term thymosin treatment on the longevity of normal mice and on the senescense of the immune response in normal and thymectomized mice; (2) To determine the effects of short-term thymosin treatment on the immune capability of aged mice. Parameters of the immune system in mice which will be evaluated include measured of both humoral and cellular immunity, such as induction of plaque forming cytotoxic effector cells, helper and suppressor function and recognition of modified-self antigens. Changes in the levels of T-cell markers and enzymes such as terminal deoxynucleotidyl transferase (TdT) and 20 alpha-steroid dehydrogenase will also be studied; (3) To evaluate the correlation between aging and immunological parameters which reflect the status of thymic-dependent immunity in man. Emphasis will be placed on aged individuals and patients with immune mediated diseases such as rheumatoid arthritis. Tests will include the determination by radioimmunoassay of serum thymosin levels, the measurement of lymphocytotoxic factors in plasma, and the measurement of the immunological reactivity of peripheral blood lymphocytes such as mixed lymphocyte reactions, cell mediated lympholysis and suppression of immunoglobulin production.